GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin

Abstract

The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disrupts Golgi stack formation and impairs critical functions of the Golgi, such as accurate protein glycosylation and sorting. However, how Golgi destruction affects other cellular activities is so far unknown. Here, we report that depletion of GRASP proteins reduces cell attachment and migration. Interestingly, GRASP depletion reduces the protein level of α5β1 integrin, the major cell adhesion molecule at the surface of HeLa and MDA-MB-231 cells, due to decreased integrin protein synthesis. GRASP depletion also increases cell growth and total protein synthesis. These new findings enrich our understanding on the role of the Golgi in cell physiology and provide a potential target for treating protein-trafficking disorders.

Golgi Structure and Function in Health, Stress, and Diseases

“…Consistently, Golgi fragmentation in AD enhances APP trafficking and Aβ production, while rescue of the Golgi causes APP accumulation in the Golgi and reduces Aβ secretion (Joshi et al 2014). Most recently, we have obtained evidence that Golgi structure disassembly by GRASP depletion reduces cell attachment and migration while accelerating cell growth and cell cycle progression (Ahat et al 2019). It will be interesting to investigate how Golgi fragmentation enhances cancer cell proliferation and metastasis in the future.…”

Phosphatidylinositol 4-kinase III beta regulates cell shape, migration, and focal adhesion number

“…, 1982 ) and functional alterations of the Golgi affect migration ( Xing et al. , 2016 ; Ahat et al. , 2019 ), we next investigated whether or not PI4KIIIβ depletion affected Golgi appearance.…”

Side chain effect in the modulation of αvβ3/α5β1 integrin activity via clickable isoxazoline-RGD-mimetics: development of molecular delivery systems

“…In addition, to confirm that compound 31 is internalized through an active mechanism of endocytosis, K562 cells were exposed for 2 h to monensin (2 µM), which blocks the trafficking of α 5 integrin from the Golgi stack to the trans Golgi network 49 . Inhibition of integrin trafficking prevented compound 31 internalization in K562 cells (Fig.…”